APPLICANT'S ABSTRACT: This research proposes to quantify the neuroanatomic abnormalities underlying neuropsychological deficits among people with brain damage caused by prenatal alcohol exposure. Although Fetal Alcohol Syndrome (FAS) is a distinct diagnostic entity, it conceals substantial variability of deficit. Furthermore, many others with prenatal alcohol exposure exhibit dysfunctional behaviors that appear to be CNS-based, but do not have facial manifestations of FAS. These are referred to as possible Fetal Alcohol Effects (FAE). We hypothesize that: (1) New image analysis methods will reveal significant mean differences in brain form between FAS and Controls that are not due solely to microcephaly and are not detectable from clinically-read magnetic resonance image (MRI); (2) Neuropsychological testing will demonstrate significant differences in the neuropsychological profiles of FAS vs. Controls; (3) The average FAE brain and behavior will more closely resemble the average FAS brain and behavior than that of Controls; (4) There are significant correlations between brain dysmorphology and neuropsychological deficits; and (5) These associations will be strong enough to classify the extent of damage and predict prognosis in the individual case. Over 5 years we plan to: 1. Gather MRI data (including landmark locations) and neuropsychological data on 180 research subjects in three groups (60 with FAS, 60 with FAE, and 60 Controls group-matched for age, sex and race.) 2. Characterize 2D and 3D differences in shapes of landmark configurations and other patterns of differences in MRI's among these groups, with due attention to age, sex and ethnicity. 3. Characterize differences in neuropsychologic profiles among the three groups, controlling of IQ as well as to age, sex and ethnicity. 4. Determine those aspects of brain shape variation and focal anatomic abnormalities most highly associated with profiles of specific neuropsychological deficit within and among groups. 5. Combine the findings from Aims 2-4 into clinically useful protocols for the detection of individuals with brain damage from prenatal alcohol exposure. This will be the first systematic study to utilize new morphometric methods to localize neuroanatomic abnormalities associated with neuropsychological deficits in patients with FAS/FAE. Detecting neuroanatomic anomalies will permit proper identification and appropriate service delivery to these patients.